Abstract
Aim:
To evaluate the effects of tanshinone IIA (Tan IIA), a lipophilic diterpene from the Chinese herb Salvia miltiorrhiza, on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits.
Methods:
LPS-induced DIC model was made in adult male New Zealand rabbits by continuous intravenous infusion of LPS (0.5 mg/kg) via marginal ear vein for 6 h. The animals were simultaneously administered with Tan IIA (1, 3 and 10 mg/kg) or heparin (500 000 IU/kg) through continuous infusion via the contralateral marginal ear vein for 6 h. Before and 2 and 6 h after the start of LPS infusion, blood samples were taken for biochemical analyses.
Results:
Continuous infusion of LPS into the rabbits gradually impaired the hemostatic parameters, damaged renal and liver functions, increased the plasma TNF-α level, and led to a high mortality rate (80%). Treatment of the rabbits with Tan IIA dose-dependently attenuated the increase in activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin-fibrinogen degradation products (FDP); ameliorated the decrease in plasma levels of fibrinogen and platelets; and reversed the decline in activity of protein C and antithrombin III. Meanwhile, the treatment significantly suppressed the increase in the plasma levels of aminotransferase, creatinine and TNF-α, and led to much lower mortality (46.7% and 26.7% for the medium- and high-dose groups). Treatment of the rabbits with the high dose of heparin also effectively improved the hemostatic parameters, ameliorated liver and renal injuries, and reduced the plasma level of TNF-α, and significantly reduced the mortality (33.3%).
Conclusion:
Tan IIA exerts a protective effect against DIC in rabbits.
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References
Markwardt F, Nowak G, Meerbach W, Rudiger KD . Studies in experimental animals on disseminated intravascular coagulation (DIC). Thromb Diath Haemorrh 1975; 34: 513–21.
Wilde JT, Roberts KM, Greaves M, Preston FE . Association between necropsy evidence of disseminated intravascular coagulation and coagulation variables before death in patients in intensive care units. J Clin Pathol 1988; 41: 138–42.
Levi M, ten Cate H . Disseminated intravascular coagulation. N Engl J Med 1999; 341: 586–92.
Klein HG, Bell WR . Disseminated intravascular coagulation during heparin therapy. Ann Intern Med 1974; 80: 477–81.
Lei XL, Chiou GC . Studies on cardiovascular actions of Salvia miltiorrhiza. Am J Chin Med 1986; 14: 26–32.
Wang N, Luo HW, Niwa M, Ji J . A new platelet aggregation inhibitor from Salvia miltiorrhiza. Planta Med 1989; 55: 390–1.
Liu JQ, Lee TF, Miedzyblocki M, Chan GC, Bigam DL, Cheung PY . Effects of tanshinone IIA, a major component of Salvia miltiorrhiza, on platelet aggregation in healthy newborn piglets. J Ethnopharmacol 2011; 137: 44–9.
Wan JM, Sit WH, Lee CL, Fu KH, Chan DK . Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury. Int Immunopharmacol 2006; 6: 750–8.
Ji HS, Yu F, Yang J . Comparative research on pharmacodynamics of Danshen co-microemulsion on hemorheology in rats with hyperlipidemia. Zhong Yao Cai 2008; 31: 566–9.
Lin X, Qi JZ, Qiu PX, Chen JS . Effect of compound Salvia miltiorrhiza injection on LPS-induced disseminated intravascular coagulation in rabbits. Chin J Pathophysiol 2011; 27: 464–8.
Lin X, Liang XX, Chen JS, Chen Q, Qiu PX, Yan GM . The effect of fibrinolytic enzyme FIIa from Agkistrodon acutus venom ondisse minated intravascular coagulation in rabbits. Transl Res 2007; 150: 295–302.
Levi M, ten Cate H, van der Poll T, van Deventer SJ . Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 1993; 270: 975–9.
Warr TA, Rao LV, Rapaport SI . Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. Blood 1990; 75: 1481–9.
Zeerleder S, Hack CE, Wuillemin WA . Disseminated intravascular coagulation in sepsis. Chest 2005; 128: 2864–75.
Hathcock JJ . Flow effects on coagulation and thrombosis. Arterioscler Thromb Vasc Biol 2006; 26: 1729–37.
Sakata Y . Treatment of DIC associated with myelogenous leukemia. Nihon Rinsho 2009; 67: 1978–83.
Oh D, Jang MJ, Lee SJ, Chong SY, Kang MS, Wada H . Evaluation of modified non-overt DIC criteria on the prediction of poor outcome in patients with sepsis. Thromb Res 2010; 126: 18–23.
Taveira da Silva AM, Kaulbach HC, Chuidian FS, Lambert DR, Suffredini AF, Danner RL . Brief report: shock and multiple-organ dysfunction after self-administration of Salmonella endotoxin. N Engl J Med 1993; 328: 1457–60.
Fong Y, Tracey KJ, Moldawer LL, Hesse DG, Manogue KB, Kenney JS, et al. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med 1989; 170: 1627.
Schabbauer G, Tencati M, Pedersen B, Pawlinski R, Mackman N . PI3K-Akt pathway suppresses coagulation and inflammation in endotoxemic mice. Arterioscler Thromb Vasc Biol 2004; 24: 1963–9.
Cataldegirmen G, Zeng S, Feirt N, Lppagunta N, Dun H, Qu W, et al. RAGE limits regeneration after massive liver injury by coordinated suppression of TNF-α and NF-κB. J Exp Med 2005; 201: 473–84.
Levi M . Disseminated intravascular coagulation: what's new? Crit Care Clin 2005; 21: 449–67.
Fujishima Y, Yokota K, Sukamoto T . The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. Thromb Res 1998; 91: 221–7.
Hamano S, Kinukawa M, Komatsu H, Miyata H, Sakuragawa N . Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models. Nihon Yakurigaku Zasshi 1991; 98: 53–62.
Acknowledgements
This project was supported by the National Natural Science Foundation of China (No 81000209), the Key Project of the Chinese Ministry of Education (No 210255), and the Fundamental Research Funds for the Central Universities (No 21609304). The authors declare that they have no competing financial interest in Tan IIA.
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Wu, Lc., Lin, X. & Sun, H. Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC). Acta Pharmacol Sin 33, 1254–1259 (2012). https://doi.org/10.1038/aps.2012.84
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DOI: https://doi.org/10.1038/aps.2012.84
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